Cell therapy for tendinitis, experimental and clinical report

To compare cultured bone marrow mesenchymal cells (cBMSC), bone marrow mononucleated cells (BMMNCs), and placebo to repair collagenase-induced tissue damage in an equine model of experimental tendonitis, 6 Standardbred horses with no signs of previous SDF tendon injury have been recruited. Three weeks after collagenase treatment an average of either 5.5 × 106 cBMSCs or 122.3 × 106 BMMNCs, saline solution (placebo) or fibrin glue were injected intralesionally in random order. Horses were stall rested for 21 weeks, and tendon ultrasound scans performed before and during this period. Horses were euthanized and tendons harvested for histology and immunohistochemistry. Data observed in this study showed effectiveness of cBMSC and BMMNC in regenerating tendon tissue after collagenase -induced tendonitis. Both cBMSC and BMMNC transplantation resulted in qualitatively similar regeneration of tendon extracellular matrix in terms of type I/III collagen ratio, fiber orientation, and COMP expression. After this favourable results, 20 horses were recruited referred for spontaneous lesions of the flexor tendons or the suspensory ligament. Horses were treated with autologous graft of BMMNCs.After treatment the. the exercise program allowed was 8 weeks stall rest, 4 weeks hand walking, 4 weeks trotting, 4 weeks of gradually raising of exercise level then horses were gone back to race. US characteristics of lesions started to improve at T3. CSA-l, FPS and TLS were better in all patients, with an appreciable filling of lesions indicated by a decreasing of CSA-l and increasing of TLS. When horses started the exercise program T8 tendon architecture improved, demonstrated by their longitudinal alignment and length. At T6, and persistently in later follorw-up, no lameness was evident by clinical examination. At time of writing 12 patients (60%) were go back to races, while other 8 (40%) are under controlled exercise program. Re-injury rate was assessed at 25%. All the owners judged good to excellent the outcome in term of athletic success.

[1]  D L Butler,et al.  Autologous mesenchymal stem cell-mediated repair of tendon. , 1999, Tissue engineering.

[2]  D. Butler,et al.  Use of mesenchymal stem cells in a collagen matrix for achilles tendon repair , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[3]  Rodolfo Quarto,et al.  Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. , 2003, Experimental cell research.

[4]  D. Butler,et al.  Repair of patellar tendon injuries using a cell–collagen composite , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[5]  Y. Ikada,et al.  Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells. , 2005, Biomaterials.

[6]  A. Zeiher,et al.  Intracoronary administration of autologous bone marrow‐derived progenitor cells in a critically ill two‐yr‐old child with dilated cardiomyopathy , 2009, Pediatric transplantation.

[7]  D. Gozal,et al.  Intracoronary administration of autologous bone marrow mononuclear cells after induction of short ischemia is safe and may improve hibernation and ischemia in patients with ischemic cardiomyopathy. , 2005, American heart journal.

[8]  P. Webbon,et al.  Harnessing the stem cell for the treatment of tendon injuries: heralding a new dawn? , 2005, British Journal of Sports Medicine.

[9]  D. Hodgson,et al.  Superficial digital flexor tendonitis in the horse. , 2010, Equine veterinary journal.

[10]  Hung-Fat Tse,et al.  Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation , 2003, The Lancet.

[11]  Hee Jung Park,et al.  Vascular patches tissue-engineered with autologous bone marrow-derived cells and decellularized tissue matrices. , 2005, Biomaterials.

[12]  R. Cancedda,et al.  Microenvironment and stem properties of bone marrow‐derived mesenchymal cells , 2001, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[13]  A. Goodship,et al.  Isolation and implantation of autologous equine mesenchymal stem cells from bone marrow into the superficial digital flexor tendon as a potential novel treatment. , 2010, Equine veterinary journal.

[14]  Christian Krettek,et al.  Modulation of proliferation and differentiation of human bone marrow stromal cells by fibroblast growth factor 2: potential implications for tissue engineering of tendons and ligaments. , 2005, Tissue engineering.

[15]  Rodolfo Quarto,et al.  Cell Therapy for Bone Disease: A Review of Current Status , 2003, Stem cells.

[16]  Seung‐Woo Cho,et al.  Implantation of bone marrow mononuclear cells using injectable fibrin matrix enhances neovascularization in infarcted myocardium. , 2005, Biomaterials.

[17]  M. Mastrogiacomo,et al.  Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy. , 2000, Experimental hematology.

[18]  Pankaj Sharma,et al.  Tendon injury and tendinopathy: healing and repair. , 2005, The Journal of bone and joint surgery. American volume.

[19]  J. Douglas,et al.  ENHANCED SUSPENSORY LIGAMENT HEALING IN 100 HORSES BY STEM CELLS AND OTHER BONE MARROW COMPONENTS , 2001 .

[20]  K. Shimada,et al.  Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial , 2002, The Lancet.